CD4 T cell responses are essential for host survival of Mycobacterium tuberculosis (Mtb) infection, but the properties of host protective CD4 T cells remain poorly understood. Accordingly, there are no correlates of protection against Mtb infection, which is a major barrier to developing new vaccine and therapeutic strategies. Previously, we previously found that the pulmonary effector T cell response against Mtb is composed of two major subpopulations that preferentially localize to either the lung parenchyma or lung blood vasculature. Intravascular Mtb-specific CD4 T cells display greater potential for cytokine production as well as active production of interferon-gamma (IFNg) in vivo compared to their tissue parenchymal counterparts. However, CD4 T cells with the ability to migrate into the tissue parenchyma were highly protective against Mtb infection, while CD4 T cells that were high producers of IFNg but poorly migrate into the lung displayed minimal control of the infection. Much of the work in the TBU in the past year has been to further explore these central observations on T cell immunity to Mtb infection. Given our previous results identifying protective and non-protective subsets of Mtb-specific CD4 T cells, we sought understand the factors that regulate the development of these subsets. IL-12/23p40 and Tbet, in particular, are known to be critical regulators of T cell differentiation, but apart from their role in inducing IFNg expression in CD4 T cells, not much else in understood about the impact that these molecules have on effector CD4 T cell diversity in the setting of tuberculosis. Therefore, we examined the role of antigen stimulation, IL-12/23p40, T-bet, and IFN in regulating the differentiation of pulmonary Mtb-specific CD4 T cell responses. We find that by limiting TCR stimulation after Th1 polarization (by generating high levels of intraclonal competition for cognate peptide) can dramatically suppress T-bet expression and the generation of the intravascular CX3CR1+ Th1 cells, and even facilitate the development of Mtb-specific Th17 cells. We employed t-distributed stochastic neighbor embedding (tSNE) analysis on a multicolor flow cytometry panel including intravascular staining and simultaneous examination of up to seven differentiation markers to examine the population structure of the CD4 T cell response to Mtb infection. This dimensionality-reducing algorithm allowed us to better visualize the complexity of differentiation sub-states found within the Mtb-specific Th1 response in the lungs. Indeed, we found that Il-12/23p40 and T-bet play a major role in shaping effector T cell heterogeneity during tuberculosis. In the absence of IL-12/23p40 CD4 T cells migrate into the lung, but differentiation stalls at an early effector CD73+CXCR3+ stage and intravascular CX3CR1+ late effector cells are not generated. Although, Mtb-specific CD4 T cells were incapable of producing IFNg, we found no evidence of immune-deviation into Th17 or Tfh cells. Therefore, IL-12/23p40 has many effects on Th1 cells beyond the induction of IFNg production, and counter-intuitively is required for the generation of a Th1 subset that cannot mediate control of Mtb infection in the lungs. Using Tbet-flox/flox X CD4 CRE mice, we found that selective ablation of Tbet in T cells resulted in nearly identical host-susceptibility to Mtb infection as intact Tbet KO mice, indicating that T cell intrinsic T-bet was responsible for almost all of the host-protective effects of T-bet. This was likely due to the near complete absence of IFNg production by CD4 T cells in the absence of Tbet. Unlike IL-12/23p40 deficient mice where there is no evidence of altered T cell polarization to other effector lineages, the Mtb-specific CD4 T cell response in Tbet-/- mice dramatically diverted to RORt+ Th17 cells with a CD69+CD103+ Trm-like phenotype, indicating that Tbet is essential to oppose Th17 induction in Mtb infection. IL-17 blockade in Tbet-/- mice resulted in slightly early time-to-moribundity, indicating that the resulting Th17 cells are weakly protective against Mtb. Importantly, the non-protective intravascular CX3CR1+ subset of Th1 cells is completely absent in T-bet deficient mice, and the overall fraction of the CD4 T cell response localized to the lung parenchyma is actually greatly increased. Therefore, the classic Th1 lineage specifying transcription factor is indeed required for Th1 lineage induction and prevention of immune-deviation to unprotective effector fates, but also promotes the generation of a large population of highly-polarized, CX3CR1+ intravascular effectors T cells that cannot mediate control of Mtb infection. We also investigated the role of IFNg itself in regulating Th1 differentiation in Mtb infection. Interestingly, CD4 T cell-derived IFN has an opposing effect compared to IL-12/23p40 and Tbet, limiting the accumulation of the non-protective intravascular KLRG1+CX3CR1+ CD4 T cells. However, tSNE analysis showed that for the large part there was a great deal of overlap in the various subsets of T cell generated in WT and Tbet KO mice, indicating that the overall differentiation was not altered in IFNg KO mice but rather the accumulation of the intravascular effector cells. In fact, suppression of the intravascular subset was dose dependent, CD4 T cells that over-produce IFNg differentiated displayed defect in generating intravascular KLRG1+ CD4 T cells compared to WT CD4 T cells. Collectively, these data show that the classic Th1-inducing factors IL-12/23p40 and T-bet which are required for host-survival also have unexpected negative effects on the protective capacity of Mtb-specific CD4 T cells by favoring the development of a large population of terminal effector-like CX3CR1+ Th1 cells that cannot contribute to control of pulmonary infection. Therefore, T cell polarizing activities of the IL-12/23p40 and Tbet must be restrained in order to produce populations of effector T cells with optimal lung-homing and host-protective ability during Mtb infection.